Browsing by Subject "Medical Oncology"

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    Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients.
    (Bone marrow transplantation, 2012-03) Mynarek, M; Tolar, J; Albert, MH; Escolar, ML; Boelens, JJ; Cowan, MJ; Finnegan, N; Glomstein, A; Jacobsohn, DA; Kühl, JS; Yabe, H; Kurtzberg, J; Malm, D; Orchard, PJ; Klein, C; Lücke, T; Sykora, K-W
    Alpha-mannosidosis is a rare lysosomal storage disease. Hematopoietic SCT (HSCT) is usually recommended as a therapeutic option though reports are anecdotal to date. This retrospective multi institutional analysis describes 17 patients that were diagnosed at a median of 2.5 (1.1-23) years and underwent HSCT at a median of 3.6 (1.3-23.1) years. In all, 15 patients are alive (88%) after a median follow-up of 5.5 (2.1-12.6) years. Two patients died within the first 5 months after HSCT. Of the survivors, two developed severe acute GvHD (>=grade II) and six developed chronic GvHD. Three patients required re-transplantation because of graft failure. All 15 showed stable engraftment. The extent of the patients' developmental delay before HSCT varied over a wide range. After HSCT, patients made developmental progress, although normal development was not achieved. Hearing ability improved in some, but not in all patients. We conclude that HSCT is a feasible therapeutic option that may promote mental development in alpha-mannosidosis.
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    An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer.
    (PLoS One, 2008-04-02) Salter, Kelly H; Acharya, Chaitanya R; Walters, Kelli S; Redman, Richard; Anguiano, Ariel; Garman, Katherine S; Anders, Carey K; Mukherjee, Sayan; Dressman, Holly K; Barry, William T; Marcom, Kelly P; Olson, John; Nevins, Joseph R; Potti, Anil
    BACKGROUND: A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective. METHODS AND RESULTS: Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide) chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%). When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06). Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8%) of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04), representing a viable alternative therapy. CONCLUSIONS: Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding microRNA and mRNA expression profiles. Importantly, we also present evidence to support the concept that analysis of molecular variables can present a rational strategy to identifying alternative therapeutic opportunities.
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    Interactive or static reports to guide clinical interpretation of cancer genomics.
    (Journal of the American Medical Informatics Association : JAMIA, 2018-05) Gray, Stacy W; Gagan, Jeffrey; Cerami, Ethan; Cronin, Angel M; Uno, Hajime; Oliver, Nelly; Lowenstein, Carol; Lederman, Ruth; Revette, Anna; Suarez, Aaron; Lee, Charlotte; Bryan, Jordan; Sholl, Lynette; Van Allen, Eliezer M

    Objective

    Misinterpretation of complex genomic data presents a major challenge in the implementation of precision oncology. We sought to determine whether interactive genomic reports with embedded clinician education and optimized data visualization improved genomic data interpretation.

    Materials and methods

    We conducted a randomized, vignette-based survey study to determine whether exposure to interactive reports for a somatic gene panel, as compared to static reports, improves physicians' genomic comprehension and report-related satisfaction (overall scores calculated across 3 vignettes, range 0-18 and 1-4, respectively, higher score corresponding with improved endpoints).

    Results

    One hundred and five physicians at a tertiary cancer center participated (29% participation rate): 67% medical, 20% pediatric, 7% radiation, and 7% surgical oncology; 37% female. Prior to viewing the case-based vignettes, 34% of the physicians reported difficulty making treatment recommendations based on the standard static report. After vignette/report exposure, physicians' overall comprehension scores did not differ by report type (mean score: interactive 11.6 vs static 10.5, difference = 1.1, 95% CI, -0.3, 2.5, P = .13). However, physicians exposed to the interactive report were more likely to correctly assess sequencing quality (P < .001) and understand when reports needed to be interpreted with caution (eg, low tumor purity; P = .02). Overall satisfaction scores were higher in the interactive group (mean score 2.5 vs 2.1, difference = 0.4, 95% CI, 0.2-0.7, P = .001).

    Discussion and conclusion

    Interactive genomic reports may improve physicians' ability to accurately assess genomic data and increase report-related satisfaction. Additional research in users' genomic needs and efforts to integrate interactive reports into electronic health records may facilitate the implementation of precision oncology.
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    Standardizing clinical trials workflow representation in UML for international site comparison.
    (PLoS One, 2010-11-09) de Carvalho, Elias Cesar Araujo; Jayanti, Madhav Kishore; Batilana, Adelia Portero; Kozan, Andreia MO; Rodrigues, Maria J; Shah, Jatin; Loures, Marco R; Patil, Sunita; Payne, Philip; Pietrobon, Ricardo
    BACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows.
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    The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond.
    (Future oncology (London, England), 2018-12) Smith, Brigid M; Duncan, Francesca E; Ataman, Lauren; Smith, Kristin; Quinn, Gwendolyn P; Chang, R Jeffrey; Finlayson, Courtney; Orwig, Kyle; Valli-Pulaski, Hanna; Moravek, Molly B; Zelinski, Mary B; Irene Su, H; Vitek, Wendy; Smith, James F; Jeruss, Jacqueline S; Gracia, Clarisa; Coutifaris, Christos; Shah, Divya; Nahata, Leena; Gomez-Lobo, Veronica; Appiah, Leslie Coker; Brannigan, Robert E; Gillis, Valerie; Gradishar, William; Javed, Asma; Rhoton-Vlasak, Alice S; Kondapalli, Laxmi A; Neuber, Evelyn; Ginsberg, Jill P; Muller, Charles H; Hirshfeld-Cytron, Jennifer; Kutteh, William H; Lindheim, Steven R; Cherven, Brooke; Meacham, Lillian R; Rao, Pooja; Torno, Lilibeth; Sender, Leonard S; Vadaparampil, Susan T; Skiles, Jodi L; Schafer-Kalkhoff, Tara; Frias, Oliva J; Byrne, Julia; Westphal, Lynn M; Schust, Danny J; Klosky, James L; McCracken, Kate A; Ting, Alison; Khan, Zaraq; Granberg, Candace; Lockart, Barbara; Scoccia, Bert; Laronda, Monica M; Mersereau, Jennifer E; Marsh, Courtney; Pavone, Mary Ellen; Woodruff, Teresa K
    Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.